HLA typing was performed on lymphocytes from patients with a common disease or family where one or more individuals show a common disease type. One hundred thirty individuals with mycosis fungoides were HLA typed. A significant increase in the HLA-B35 antigen as well as HLA-DR5 was found in effected individuals compared to the normal population. HLA typing of 7 multiplex families with members having melanoma or premalignant mole syndrome showed no linkage with the major histocompatibility complex (MHC). These data contradict earlier reports suggesting MHC association with this disease. Families with adult T-cell leukemia and HTLV-I infection (serum antibodies) were found to have a low level of linkage to MHC (code score 1.5). Patients with acquired immunodeficiency syndrome (AIDS) showed an increased frequency of HLA-DR5, MT2 in the patients with Kaposi's sarcoma. Individuals at risk for this disease (male homosexuals) who have antibodies to HTLV-III, had an increase in HLA-DR-4 compared to the normal frequency of this antigen and to the frequency of DR4 in AIDS patients. Regulation of HLA-DR expression was studied in context with HTLV-I infection. Resting ATL (adult T-cell leukemia) cells expressed little or no HLA-DR. Activation of the HTLV-I retrovirus caused a complementary increase in HLA-DR mRNA, while DNA methylation remained the same. The results indicate that post-transcriptional control of HLA-DR expression may be influenced by viral replication.